Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior

Advanced neuroblastoma and malignant liver tumor are representative childho od cancers for which combined chemotherapy including cisplatin and doxorubi cin is routinely performed, The prognosis of patients with tumors which dev elop multiple drug resistance (MDR) is unfavorable. To elucidate the role o f multidrug resistance-associated protein (MRP) and canalicular multispecif ic organic anion transporter (cMOAT) in the clinical behavior of the tumors , we examined 42 neuroblastomas and 10 malignant liver tumors for the expre ssions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR) . The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated, We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship bet ween MRP expression and the patients' outcome, The forced expression of N-m yc failed to enhance the expression of MRP in N-myc transfected neuroblasto ma cell lines, cMOAT was rarely expressed in the neuroblastomas, but was fr equently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced express ion of these genes might be characteristic of childhood malignant liver tum ors and related to their clinical chemoresistance.